The proposed work is ultimately directed to elucidating the biophysical basis of nervous dysfunction in demyelinating disease. Changes will be sought in the pattern of distribution of sodium channels and sodium pumps in the nerve membrane during the processes of normal myelination (in the newborn animal) and of demyelination, produced experimentally in a number of ways. A variety of electrophysiological and pharmacological techniques will be used. Voltage-clamp experiments will be done to determine the Hodgkin-Huxley parameters for mammalian myelinated nerve. Based on the above results, a computer model will be used to examine the consequences of the altered excitability properties of demyelinated nerve. These electrophysiological consequences of demyelination will also be examined experimentally. BIBLIOGRAPHIC REFERENCES: Ritchie, J. M. & Rogart, R. B. (1976). Physiological basis of conduction in myelinated nerve fibers. In: Myelin (P. Morell, ed.), Chapter 1, Plenum Press, N. Y. (In the press). Ritchie, J. M. & Rogart, R. B. (1976). Pathophysiology of conduction in demyelinated nerve fibers. In: Myelin (P. Morell, ed.), Chapter 2, Plenum Press, N. Y. (In the press).